The vertebrate brain evolved to control movements and thereby achieve biological goals, including procreation, harm avoidance, ingestion of essentials, exploration, and energy economics. To cope with changing conditions, early vertebrates developed, and their descendants inherited, the ability to expand their innate repertoire of motor capabilities. This facility, called motor skill learning, increased their ability to attain biological goals through interaction with the environment. What motor skill learning did for our ancestors 500 million years ago, it does for us today. In advanced mammals, a great deal of our motor learning mechanism is housed in the motor areas of the frontal lobe and the parts of the cerebellum and basal ganglia directly connected with then. Accordingly, the Section on Neurophysiology studies the frontal cortex and related parts of the brain, such as the basal ganglia, in motor learning and planning. This project builds on the monograph published by MIT Press by Shadmehr and Wise (2005), which presents a new theory of motor learning in a biological and evolutionary context. Motor skill learning improves our ability to achieve goals by improving the spatial and temporal accuracy of our movements. The motor system learns how the body interacts with the world, and uses this knowledge to plan movements and to produce the forces needed to reach targets. It does so, in part, by learning to correct both previous and ongoing errors. Neural networks involving the motor cortex and cerebellum correct errors made on previous movements, whereas overlapping networks involving the motor cortex and basal ganglia correct ongoing movements. The motor system thereby leads to the production of forces needed to reach single or sequential targets (Wise and Willingham, 2007). To gain information on the neural mechanisms of such learning, we studied intermanual transfer of a newly learned motor skill using the serial reaction-time task (SRTT). Sixteen, right-handed volunteers trained a 12-item sequence of key presses repeated without the participants knowledge (Perez et al., 2007). Random sequences were also presented as a control condition. Response times improved in random and training blocks in both hands. The former improvement reflects the nonspecific learning of a general response skill; the latter, a specific learning of a sequential action series. Overall, participants who performed the random and sequence blocks faster with the right (learning) hand by the end of the training were also the fastest with the left hand on the transfer test (r=0.75 and r=0.77, respectively). They also showed less interhemispheric inhibition (IHI) after training (r=0.66), as assessed by the effects of a conditioning transcranial magnetic stimulus to the contralateral primary motor cortex on the effects of a test stimulus of homotopic area in the transfer hemisphere. This correlation was not present with IHI values obtained before training. However, no correlation was found between sequence-specific transfer and IHI. This result shows that interhemispheric interactions between the two primary motor areas involve mostly the nonspecific aspects of motor learning, and that other areas mediate the sequence-specific transfer. A follow-up series of studies (under review at the time of this report) pointed to the supplementary motor area and its principal relay nucleus in the thalamus for this sequence-specific transfer. In a neuroimaging component of this research, the magnitude of intermanual transfer correlated with activity in both the SMA and the ventrolateral anterior (VLa) thalamic nucleus, the principal relay of information from the basal ganglia to the SMA. These findings suggest the involvement of SMA and VLa as neural substrates underlying the intermanual transfer function of the specific training sequence. The link to basal ganglia is important because of its well-established role in motor selection, learning and planning and, as noted above, the online adjustment of action. These functions include learning, memory, skill, planning, switching, sequencing, timing, and the processing of rewards and other feedback. In a review article for the New Encyclopedia of Neuroscience, we put forward the idea that the basal ganglias contribution can perhaps best summarized as a device that resolves the selection demands that confront a behaving organism: much as it likely did for the earliest vertebrates. These demands require prioritizing, scheduling, planning, sequencing and generally controlling the way in which context elicits behavior in accordance with external and internal constraints (Aron et al., 2007). In addition to the role of the SMA in transfer of sequential knowledge, we have argued that a different nonprimary motor area, the ventral premotor cortex, plays a different and complementary role. Wise (2006, 2007) developed the idea that ventral premotor cortex computes the difference between hand position and target location in a coordinate frame based on vision (as detailed in the Shadmehr and Wise, 2005, monograph mentioned above). Our theory showed furthermore that this computation could support visually guided reaching and pointing, generally, as well as head orientation during social signaling.